Drugs affecting the neuromuscular junction Flashcards
What processes may drugs affect at a cholinergic synapse (presynaptic)?
Synthesis of ACh
Movement of ACh into vesicles
Choline transporter
Exocytosis of vesicles
What stops the synthesis of ACh?
Cholinacetyltransferase
What stops the transport of ACh into vesicles?
Vesamicol
What stops choline transporters?
Hemicholinium
What stops exocytosis of vesicles?
Toxins
What is botulinum toxin?
Clostridium botulinum
2 subunits:
- 1st binds to presynaptic membrane
- 2nd cleaves proteins involved in exocytosis
Block of cholinergic synapses results in muscle death
Used as wrinkle remover
What are the two categories of post-synaptic drugs and what do they act upon?
Non-depolarising
Depolarising
Nicotinic AChR
How do non-depolarising drugs work?
Competitive antagonists at nAChRs
Lower endplate potential
Used as an adjunct to anaesthesia
Give an example of a non-depolarising drug
D-tubocurarine
How do depolarising blockers work?
Agonist at nAChRs
Cause endplate depolarisation
Increases action potentials
Uncoordinated, fine contractions (fasciculations)
Prolonged depolarisation inactivates voltage-gated Na+ channels
Name a depolarising blocker
Suxamethonium
When are depolarising blockers used?
Brief procedures
What breakdown depolarising blockers?
Plasma cholinesterase
What are some unwanted affects of depolarising blockers?
Bradycardia
K+ release
Intraocular pressure increases
Prolonged paralysis if enzyme is in short supply
What are a phase 1 and 2 block?
Phase 1: Inactivation of Na+ voltage gated channels
Phase 2: Inactivation of nAChRs
What is a cholinesterase inhibitor?
Interacts with AChE and plasma cholinesterase
Prevents breakdown of ACh
Enhances synaptic function
Affects other synapses where ACh is the transmitter such as autonomic ganglia and postganglionic parasympathetic nerves
Explain how the different interactions of the cholinesterase inhibitor is related to their longevity
Edrophonium interacts with the enzyme ionically and effects last for a few minutes
Neostigmine interacts with the enzymes covalent bonds and effects last for a few hours
Organophosphates phosphorylate the enzyme which is irreversible
What are organophosphates used for?
Pesticides
Chemical weapons
How do cholinesterase inhibitors and non-depolarising blockers interact?
They reverse the effect of non-depolarising blockers
End plate potential is raised
What is myasthenia gravis?
Autoimmune disease
Antibody produced against nicotinic AChR
Muscle weakness
Eventually leads to death
When are anticholinesterases needed?
Treatment of myasthenia gravis to increase ACh levels and subsequently improve muscle function
